Endoplasmic Reticulum Stress Promotes Telomerase Reverse Transcriptase Expression Contributes to Development of Allergic Rhinitis.

Background: The Th2 cell polarization is a crucial factor in the pathogenesis of allergic diseases. The underlying mechanism requires further investigation. Telomerase has an immune-regulating ability. The aim of this study is to elucidate the association between telomerase and Th2 cell polarization in patients with allergic rhinitis (AR).

Methods: CD4⁺ T cells were isolated from blood samples collected from AR patients and healthy control subjects. RNA sequencing was employed to analyze RNA samples extracted from CD4⁺ T cells. An AR mouse model was established using the ovalbumin-alum protocol.

Results: High telomerase gene activity and high endoplasmic reticulum (ER) stress status were observed in CD4⁺ T-cells in patients with AR. Positive correlation between the telomerase reverse transcriptase (TERT) gene expression in CD4⁺ T cells and AR response in patients with AR. TERT facilitated the degradation of Foxp3 proteins in CD4⁺ T cells, resulting in the polarization of Th2 cells. Sensitization with the ovalbumin-alum protocol enhanced the Tert expression in CD4⁺ T cells by exacerbating ER stress. Conditional inhibition of the Tert or eukaryotic translation initiation factor 2-α (Eif2a) expression in CD4⁺ T cells effectively attenuated experimental AR in mice.

Conclusions: Elevated amounts of telomerase in CD4⁺ T cells were found in CD4⁺ T cells of subjects with AR. Telomerase promoted Th2 cell polarization by inducing Foxp3 protein degradation and promotes GATA3 activation. Inhibition of TERT or eIF2a alleviated experimental AR.